The 2015 Dietary Guidelines have been released, and some supposedly significant changes, advised. Cholesterol intake is no longer limited. Saturated fat is to represent < 10% of daily caloric intake. Sustainability considerations are now to be considered. Simple sugars are anathema and caffeine is okay. Vegetables and fruits remain highly emphasized. Has much changed? Not really. Most of us in Cardiology and Lipidology dropped the cholesterol ban a decade ago. We typically emphasize fresh fruits and vegetables, low fat meat that is organic and devoid of antibiotics, and a limitation of simple sugar. Most of us don’t consider sustainability issues when advising our individual patients. Many of us believe that world issues – including economics – should stay out of the exam room and remain in the courtroom. (I am a member of that camp). But what is the layperson to do with these Guidelines? Does he or she have to make dramatic changes in his or her diet? The answer of course depends upon the individual patient’s status. Is weight loss necessary; does the patient have cardiovascular disease or very high LDL cholesterol, for instance? Let’s first look at the history of man, briefly examine the state of dietary literature, and then make some generalizations.

Anthropology unequivocally demonstrates that human beings are omnivores. In fact, all of our primate relatives also rely upon meat in the wild. They even need it in captivity. When the Washington DC Zoo attempted to breed the Amazon Golden Marmoset monkey, they failed miserably. It was not until meat was added to their diet that the monkeys begin to thrive and reproduce. Since the beginning of our tour on earth we have also eaten meat. In fact, for the first 4 million years of our existence, meat was our main source of nourishment. About 10,000 years ago we introduced farming and animal husbandry. Most farming was done to feed our animals as they represented our most desirable food source. Recently we have fallen prey to our own impact on nourishment – we have started processing, and ruining, our food. Sugar has been added; nutrients have been stripped from grains; grains are squeezed (instead of eaten whole) to produce oils; and animals have been raised in pens, limiting their ability to develop lean muscle mass, and also often requiring the introduction of antibiotics. We have created a food supply that is most likely killing us.

In response to our understanding of the role cholesterol plays in heart disease – and it does play a significant one – we have introduced guidelines to try to reduce cholesterol. Saturated fat eaten to excess does raise LDL (not a good thing), but cholesterol consumption has little impact on our LDL levels. Therefore the current Guidelines did what was appropriate and removed restrictions on cholesterol consumption while maintaining limitations on saturated fat. They also appropriately implore us to eschew sugar. No one will argue against the latter recommendation (except perhaps the sugar industry). But are there studies to support such advice? Unfortunately, beyond PrediMed (which demonstrated the cardiovascular advantage of a Mediterranean diet) no high level studies have been performed. Many observational studies exist, but doing a solid dietary trial is actually immensely difficult. Thus we are left to rely upon our understanding of basic science, animal experiments, pathophysiology, and anthropology. The conclusion for most of us I believe follows Aristotle’s ancient tenet of moderation. We should consume natural foods whenever possible, avoid processed foods, eat copious quantities of vegetables, consume ample fruit, and don’t worry so much about consuming lean meat, fatty fish, and some chicken as well. We should do this in the context of seeing our physicians, discussing our own personal issues, and modifying our diets to adjust to individual needs when indicated. Eating has become a complex endeavor, yet it ought to be much more straightforward. What we need though is access to the aforementioned natural food, the type of food that has been unscathed by human hands. And therein, unfortunately, lies the rub.

In a perfect world with boundless resources, patients would always have access to every doctor’s prescription. But our world is not perfect and our nation is in deep debt. Consequently every day doctors across the country receive denials for medications and procedures that we have prescribed. We know our patients need these medical interventions yet our hard earned positions as practicing physicians (requiring decades of study) are no match for the far less qualified employees of insurance companies. Oftentimes our prescriptions are lifesaving. Yet we are told patients can’t have what we’ve ordered. What we have ordered is simply “too costly”. We are forced to choose something else, even if it is an inferior approach and leaves our patients – those people we have all sworn oaths to protect – relatively unprotected. So, with resources limited to such a degree that we have lost access to solutions we know to be beneficial, what are doctors and patients to do? Let’s look at a disorder deserving great attention and intervention; yet oftentimes remaining hidden in the shadows. The disease is called FH (Familial Hypercholesterolemia) and it occurs in about 1 out of every 200 people.

One of the disorder’s characteristics that makes it difficult to diagnose is the wide variation in how it manifests; some people have LDL cholesterol levels well over 200 (I’ve seen levels over 500) while others are not so badly impacted. Some patients have heart attacks in their teens while others never experience such premature disease. One of modern day medicine’s most well established “facts” is that the lower a person’s LDL, the less likely he or she is to have a heart attack or stroke. Now consider those individuals with FH in whom we simply cannot, no matter how hard we try, adequately reduce their LDL utilizing insurance approved modalities such as statins and dietary modifications. Such people may have already suffered heart attacks at very young ages. They are at extraordinary risk for a future heart attack or stroke. Yet, their insurance carriers still often create impenetrable barriers for access to additional medications as well as LDL apheresis, a method that was FDA approved in the 1990s, and lowers LDL by a whopping 70%. Carriers bemoan the costs of the medications or procedure and cite a lack of adequate “outcome data” as their reason for denial. Though doctors explain that it is now accepted as doctrine by lipid experts across the globe that lowering LDL by any means provides dramatic CVD risk reduction, they remain intransigent. We share our knowledge of Mendelian Randomization studies, which have proved beyond a shadow of a doubt (in the framework of present-day science) that lowering these patients’ LDL levels will vastly decrease their chance of suffering repeated heart attacks, strokes, stents, and bypasses. Still their ears and minds are shut. We, the doctors, are powerless. And our patients suffer the consequences. And, compounding the problem, there is currently active consideration among insurers to make it even more difficult for patients to receive LDL apheresis.

The New Year has just begun and my colleagues and I have already received a plethora of complaints from patients bemoaning the fact that their insurance carriers have increased their medication costs to such a degree that for many they can no longer afford to take them. What will happen to these patients? Will they develop unnecessary heart attacks or strokes? Will they need unwanted and otherwise preventable procedures like bypass surgery and stents? I do worry they will fare less well than had they been permitted to follow the care so cautiously outlined by their treating physicians. And medical evidence does support my concern. I believe an outcry from patients is needed. Doctors will continue to make our case, but until the voices of worried patients achieve adequate volume, I fear the status quo will reign.

Any doctor worth his salt recognizes that patients don’t always respond the way we anticipate they will. For example, utilizing the best of our scientific methodologies we know LDL is causally related to vascular disease. High LDL causes disease while low LDL mitigates it. Yet, we occasionally see patients with extraordinarily high LDL and no disease, as well as those with very low LDL and severe disease. In some circumstances, patients with a vascular disease promoting mutation – as in Familial Hypercholesterolemia – will have severe and premature heart disease while their relatives with the same mutation somehow remain unscathed. How can this be? What we’ve all come to believe is that there must be protective genes that somehow offset the detrimental aspects of other genes. Let’s dub these desired genes “Guardian Genes”.

In the case of vascular disease promoting disorders, Guardian genes cause the exception, not the rule. They Teflon coat individuals who under normal circumstances should develop heart attacks and strokes. This wonderful rarity can unfortunately lead to a misunderstanding of disease processes as well as their cures. When someone speaks of grandma whose LDL was 300 and yet lived to the ripe old age of 100, sans MI or stroke, the take-home message often is, “Those doctors don’t know what they’re talking about. LDL is not the cause of heart disease. My LDL is only 200 and as grandma lived to 100 and with worse numbers, why should I take that statin medicine. Just look at the Internet and you can see how terrible those medicines are.” Unfortunately the Guardian genes are currently merely speculative. As such we cannot identify them. And, we know that intra-family variability in development of vascular disease supports the notion that theses guardian genes are inherited entirely separately from the disease promoting genes. What that means is just because grandma won the lottery, don’t bet your life (literally) that you did as well. In my own practice I’ve seen 70-year-old parents mourn the deaths of their 40-year-old sons and daughters who died of MIs. Though they shared the same bad genes, the parents did not suffer the unfortunate (and more predictable fate) of their children.

The bottom line here is that we doctors must base our treatment recommendations on the odds. We weigh and measure the pros and cons of therapeutic options (like the statins) against the likelihood that an individual patient will develop a serious event such as a heart attack, stroke, or even death. We use our best judgment based upon many facets of knowledge and understanding. We then make our recommendations hoping to stave off future adverse cardiovascular events. We never risk a patient’s life hoping he or she has inherited a guardian gene. Until we identify the elusive lifesaver guardian genes they will remain relegated to being the modern day Holy Grail of genetics. We all pray we will find them, but until that day we must continue to practice within the limits of our understanding. And while we do, we hope our patients understand that our suggestions and recommendations are born of both a deep understanding of the science of medicine and the burning desire to help our patients live the longest and best lives possible.

The AHA 2014 Scientific Sessions are over and I have already written twice about IMPROVE IT but I feel compelled to write again. Although the media has been oddly silent about the trial (why is that I wonder???), I predict its fallout will greatly impact the disciplines of Cardiovascular Disease Prevention, Clinical Lipidology, and even the essence of clinical practice. The reasons are manifold. First, the trial proved two critical theories: a lower LDL cholesterol level is better, and statins are not the only way to achieve a clinically relevant LDL reduction. Additional key considerations from IMPROVE IT include:

Lower LDL in properly chosen patients (and probably almost everyone) yields lower rates of stroke and heart attack, the two most formidable foes of modern man. For example, in the trial, an LDL of 53 was significantly better than an LDL of 70. Should we doctors then aim for 40, or perhaps even 25?

In our high-risk patients should we consistently and continuously add medications to statins in order to drive cholesterol levels lower and lower? For example, in a patient with a prior heart attack is it now fair to accept 70 for an LDL when we know that 53 would decrease our patient’s chance of having a recurrent and potentially life-threatening event?

What do we do with the hotly debated 2013 ACC/AHA Cholesterol Guidelines? They eliminated LDL goals and allowed for the use of Zetia only with individualized – and typically time-prohibitive – clinician/patient discourse, but they did NOT encourage driving LDL lower than 70. The Guidelines advocated for an LDL response to therapy of > 50%. So where does that leave our heart patients who start with LDLs of 180, for example. If they achieve the intended LDL reduction of 50% and thereby remain with an LDL of 90 mg/dL the guidelines surely say all is well – job well done. They state there is no indication to go further. Well now there is an indication. Now we can say with certainty that an LDL of 53 is a far better goal than 90. Having an LDL of 90 leaves significant and now manageable residual risk. So then how can a health care provider in good conscience advocate keeping such a patient at an LDL that clearly conveys greater risk?

The Guidelines also strongly advocate our utilization of maximum statin doses prior to adding an agent like Zetia. Knowing that higher dose statins produce more side effects while yielding a diminishing return on cholesterol lowering, wouldn’t it now be more prudent for doctors to prescribe low dose statins in combination with Zetia? This would limit side effects while yielding lower LDL levels than would the Guideline recommended approach. More food for thought.

How will insurance providers respond to Improve-It’s results? After the ACC/AHA Guidelines’ release, with lightening speed they downgraded access to add-on therapies such as Zetia. Of course that saved them money. So what now? Will they respond in kind, follow the science, and quickly allow patients access to these medications? We shall see but I have my doubts. Profits it seems oftentimes take precedence over science and health.

One more crack at the Guidelines for now: It is true that we do not know what represents the optimal LDL cholesterol level in human beings. Based upon our ever-expanding understanding of lipids including our body’s limited need for extraneous cholesterol however, it is safe to say that that level is probably quite low, perhaps even as low as 25 or 30 mg/dL. And, given the fact that many of us are goal-oriented, wouldn’t it now make sense to join our friends across the pond as well as our very learned friends here at home in the National Lipid Association and simply reinstate LDL goals?

As I sit at my desk tapping these keys I am clearly frustrated by the politics and economics woven inextricably into the fabric of medical practice. But I am also comforted and encouraged by the knowledge that many of us have already spent the last decade and beyond practicing the way we felt the science dictated. And by so doing, in the matter of LDL-lowering with Zetia, for every 120 patients we’ve treated in an Improve-It style, we’ve saved 3 from enduring a stroke or heart attack. This fact renders all our struggles worthwhile.

On a final note let us not forget that doctors have NO financial incentive to prescribe these medications. Our only “dog in the fight” is protecting our patients from harm. Insurance providers often do have a financial incentive to preclude doctors from prescribing some medicines (typically those that cost them more money). So whom do you, the patients, want to be in control of your medication regimen – the more highly educated and clearly non-conflicted physicians, or the less knowledgeable and often-conflicted insurance carriers? The answer to me seems pretty clear.

The IMPROVE-IT verdict is in and it will change the practice of cardiovascular disease prevention. For the first time, a non-statin medication has been shown to reduce cardiovascular events (including stroke and MI) when added to a statin. Achieving an LDL level of 53 vs 70 by the end of the trial’s first year translated into a significant ASCVD risk reduction. The risk reduction is so substantial that in this patient population the “number needed to teat” was only 50. That means that for every 50 patients treated with Zetia on top of a statin, a serious/life-threatening event was prevented. And, there were no safety issues associated with adding Zetia. Thus, a downside was not present. There are so many ramifications of this trial; I will highlight a few:

As believed by most lipid (cholesterol) specialists, lower LDL is definitely better.

Many insurance companies will have to revisit their denials of Zetia – it has now been shown to be highly effective and must be a part of doctors’ armamentaria.

Other emerging medications that dramatically lower cholesterol – the PCSK9 inhibitors and possibly the CETP inhibitors – will likely lower ASCVD events in the right patients.

In patients with severe genetically caused high cholesterol – specifically those with Familial Hypercholesterolemia – doctors will try even harder to use varied tools to lower LDL as much as possible. This includes using LDL apheresis, a procedure that has frequently been denied coverage by many insurance carriers, even after experts have testified about its efficacy.

We have learned that an understanding of biology and pathophysiology, in the context of clinical experience and careful observation, should not be dismissed solely because of the absence of a large randomized controlled trial (RCT). Though it took an RCT to prove this point, those of us who have been using Zetia religiously for many years have borne witness to its efficacy. We did not need this trial to tell us how important the medication is in the management of ASCVD, but it surely makes us feel better (and a bit vindicated as well). Most consequentially, it is heartwarming to consider the vast numbers of patients we’ve helped avoid experiencing heart attacks and strokes as a result of our well-considered and steadfast convictions.

I spent Thursday and Friday in California. No, I wasn’t strolling on the beach or sipping local wines. Instead, I was engaged in strategic conversations during our FH Foundation Board of Directors Annual meeting. FH (Familial Hypercholesterolemia), as you know from prior posts, (if you don’t, please visit www.thefhfoundation.org or see my older blogs and FH/cholesterol articles at www.preventivecardiologyinc.com) is a common yet terribly underdiagnosed genetic disorder that elevates LDL cholesterol which in turn causes early and life-threatening heart disease. Affected patients cover a wide spectrum, having disease from before age ten to as late as 70 or 80 years old. We spent some time examining last year’s accomplishments, but more importantly we determined how to continue the process of converting dreams into reality. I’ve chosen to share this story with you for two reasons: First, FH must be conquered. Second and no less important, the Foundation epitomizes the power of a small group driven by unfettered passion, enthusiasm, and commitment.

Katherine Wilemon, the group’s founder, CEO, and tireless leader, suffered her heart attack shortly after the birth of her daughter. Though she had lifelong high cholesterol, and had experienced symptoms before the event, her genetic disease was initially unrecognized. And, in medicine, to be able to provide appropriate care we usually must know what it is we’re treating. Fortunately for Katherine – and her family – she survived. Subsequently, wishing to turn a terrible event into a hopeful future, Katherine started the FH Foundation. That was just three years back. Since then, Katherine has not only surrounded herself with a growing group of highly effective and devoted patients, doctors, and businesspeople, she has travelled the world building awareness and interacting with every true FH expert. The FH Foundation has established a National FH Awareness Day. It has created the first and only Registry for FH patients in the US (Cascade FH). The FH Foundation spearheaded the establishment of ICD 10 codes for this disease, and it has initiated protocols to identify every single FH patient in our nation.

Our second Global FH Summit will take place this October in New York City. An array of nations will be represented. The list goes on and on. I recount this litany of achievements not to boast, but to demonstrate how the visions of an individual can burgeon, ultimately impacting the reality of so many. Coming away from two days of inspiring meetings I am certain the Foundation will continue to succeed. In short order FH will entirely emerge from the shadows. FH will become a disease on the tip of every doctor’s tongue, and consequently afflicted patients of all ages will no longer suffer and even die unnecessarily. Millions of people’s lives will be changed for the better. At the risk of being mawkish, I must state that my experience with the FH Foundation illuminated the fact that if more of us would only act with similar commitment and intention, we might just find ourselves in a peaceful and unified world. It’s a tall order I know, but the FH Foundation has given me a glimpse of the possibilities that can be born of the seemingly impossible.

Recently, after participating in a meeting attended by a few high-powered CVD researchers I returned home plagued by a most simplistic question: What is the purpose of LDL cholesterol? Please refrain from bursting into uncontrollable spasms of laughter; I am well aware that as a clinical lipidologist I never imagined such a question would have the capacity to keep me up at night. And yet it did. And so I called my faithful counsel, upon whom I can always rely to extricate me from any lipid conundrum. Tom Dayspring responded to my query unflustered, promptly sending me articles to help me find my way. I read them and this is what I realized. LDL cholesterol is essentially garbage. The story goes something like this.

Our livers manufacture triglyceride – (TG) and cholesterol – containing lipoprotein particles called VLDLs. This is old news. VLDL contains about 80% TG and 20% cholesterol. Its purpose is to nourish our organs. As these particles pass through the tiny capillaries of our various organs, enzymes called Lipoprotein Lipase (LPL) snip the fatty acids from their TG backbone, Glycerol. This too is old news. These released fatty acids are either used for energy or stored by our organs for future needs. The shrunken down VLDL particles, devoid of most of their TG energy content, are now re-dubbed. They have become LDL particles. They are cholesterol-rich. Their content represents what most people speak about after visiting their doctors – LDL-C or LDL cholesterol. Here’s where it gets intriguing. Although any lipid specialist can tell you that every single cell in our body has the capacity to make cholesterol, most believe that the cholesterol contained in LDL particles has some greater purpose. Our cells however do not need the cholesterol contained in LDL particles; nonetheless, most of us believe they use it. This belief is untrue. LDL-C is actually not utilized to any significant degree by any organ systems in human beings. Other animals may use some of it here and there, but not us. We just don’t need it. In fact, the goal of LDL particles is to get to the liver ASAP for disposal. Otherwise, these particles tend to land in places where we do not want or need them, our blood vessel walls to be more specific. You know how that story goes – plaque forms; plaque ruptures; heart attacks or strokes ensue…

So when people tell you not to worry about your high LDL-C levels, please reconsider abandoning your doctor’s LDL-C-lowering advice. And definitely don’t worry that low LDL-C levels will deprive your cells of their much-needed cholesterol. It won’t. Your cells are quite capable of making their own supply of cholesterol. On a somewhat esoteric note, it is true that the surface of LDL particles transports some vital nutrients around the body (vitamin E for one). This fact however does not imply that more LDL is better than less. We need just a tiny bit for non-cholesterol purposes. Excess does us no good, and in truth it does us a good deal of harm.

The distillation of well over one hundred pages of two guidelines into a pragmatic and accessible tool for the practicing clinician is of course a monumental task. It is essential to do so though. Clinicians require clear guidance in helping them manage patients in harmony with scientific developments. To think though that science is simply and solely a regurgitation of large randomized double blind placebo-controlled trials would be foolhardy to say the least. Science – especially medical science – is so much more. The fast-paced evolution of science keeps us all on our toes. And there are so many levels to consider: clinical trials of all forms, basic science of multiple disciplines, clinical acumen borne of clinical experience, and of course good old-fashioned common sense. So the Guidelines’ authors’ use of just a single facet of science, the Randomized Clinical Trial (RCT), a priori limits the utility of the recent guidelines. Still, they must be addressed and reckoned with. Indeed like most other things in life, they are not “all bad.” Before distilling the Guideline’s into a practical approach that I personally intend to follow, let’s first put the premise of the RCT as “King” in a real-world context by examining a typical doctor’s approach to patients.

In medical schools, residencies, and fellowships all physicians are trained how to diagnose and manage patients. Take a hypothetical case. A new patient awaits your expertise as you enter the exam room. The patient has dutifully completed a multi-page questionnaire, the modern-day equivalent of a Review of Systems (ROS), Past Surgical History (PSH), Past Medical History (PMH), List of Allergies and Current Medications, and History of Present Illness (HPI). You’ve read the document prior to entering the room but you spend time clarifying the issues and creating this patient’s cohesive medical story. Then you examine him; from his right, just as you were taught in medical school. Your exam has morphed of course, emphasizing those aspects relevant to your particular specialty but still incorporating features from other areas of interest. After all, it is a whole person you are seeing, and ailments oftentimes breach systems’ boundaries as they are not constrained by artificial barriers. You examine his blood work as well as any other pertinent tests that have been performed prior to the visit. Then you think. You place the pieces of his particular puzzle in an orderly fashion; you make diagnoses; and then you create a plan. Reflecting on every single aspect of this fundamental, age-old doctor-patient interaction, consider how much of it is truly based upon solid RCT evidence. I will spare you the agony of this exercise as I’ve already done it countless times. The answer is essentially none. Where are the RCTs validating our ROS, HPI, examination from the right…? They simply do not exist. Yet, this is how we all practice medicine. And, it has worked out rather well for our patients. None of us should be handcuffed by RCTs when we evaluate and treat patients; we are all free to use any and all of the countless tools at our disposal. And frankly, the more tools in our chest, the better off are our patients. So, rule number one in addressing the guidelines is, “Remember that they are not rules.” Guidelines are not a part of the Ten Commandments. Even the authors of the 2013 ACC/AHA Guidelines acknowledge this when they state, “Guidelines attempt to define practices that meet the needs in most circumstances and are not a replacement for clinical judgment. The ultimate decision about care of a particular patient must be made by the healthcare provider and patient in light of the circumstances presented by that patient.” Translation: You the doctor should treat each and every individual patient in the manner you deem most appropriate. You must not feel shackled by these or any other “Guidelines.” With this in mind, I will now review the Cholesterol and Risk Assessment Guidelines to present an approach I will utilize in my practice. The views that follow emanate from experience garnered through practicing Clinical Lipidology and Preventive Cardiology, in addition to my personal interpretation of the literature as a whole.

Four groups qualify for statin therapy in the new guidelines, and I agree; they should all be treated. They are:

Primary elevations of LDL-C > 190 mg/dL (consistent with Familial Hypercholesterolemia, or FH). These patients are to receive high-intensity statins.

Diabetic patients between the ages of 40 and 75 with LDL-C 70 to 189 mg/dL and no history of ASCVD. Patients with 10 year risk > 7.5% receive high-intensity statins while others receive moderate-intensity statins.

Patients without clinical ASCVD or Diabetes Mellitus between the ages of 40 and 75, having an LDL-C 70 to 189 mg/dL and 10 year ASCVD risk of > 7.5%. These patients are to receive moderate-to-high intensity statins.

A few problems with this construct are:

The Risk calculator is still shrouded in uncertainty. Many issues remain to be resolved, not the least of which is the fact that a strong Family History of premature ASCVD fails to impact risk in this system. Also, only 24,000 patients were evaluated to construct this tool which sits at the center of these guidelines and is meant to be used to determine therapy for hundreds of millions of people. Therefore, for now, when I opt to do a 10 year risk assessment I will still use Framingham Risk Scoring. I do so with the understanding of the limitations of this scoring system and the concomitant need for methods to further risk reclassify patients.

The intention is to treat patients with high-intensity statins and assume an LDL-C reduction of > 50%, and moderate intensity statins to achieve a reduction of 30 to 50%. LDL-C goals are now passé in this paradigm. However, we all know that each patient is unique. Some respond very well to statin therapy; others do not. I will therefore continue to measure LDL-C (as well as LDL-P) on drug and I will continue to get my patients to goals at least as stringent as those in ATP3. There are ample data supporting the “lower is better” hypothesis. For example, the Cholesterol Treatment Trialists (CTT) study showed in both phases one and two that lower is better. The fact that we do not have RCTs that have used titration of statins to LDL goals as a primary endpoint in no way negates the overwhelming body of literature showing better outcomes at lower LDL-C , apo B, and LDL-P levels across a range of different statins. I will continue treat to targets.

The high-dose-statin-absent-adjunctive-therapy (or-even lipid/lipoprotein-follow-up) concept is to me “pie in the sky.” We all know that from an LDL-C – but even more so LDL-P or apo B – standpoint by prescribing statins alone we will fall woefully short of what we have been accustomed to achieve. We also know that lower is better. Thus, by adhering to the guidelines’ advice we will very possibly see worse future outcomes. Additionally, we know from several trials that statin-related Diabetes Mellitus is dose related. JUPITER found that 20 mg of Rosuvastatin reduced 2.5 ASCVD events or deaths for every one excess in DM. Thus there is a trade-off for uptitration of statins. For me, I will use statins as a base and other therapies such as cholesterol absorption inhibition and bile acid sequestration as adjunctive therapy.

ASCVD includes the presence of PAD but it does not include the presence of subclinical disease in the coronary or carotid arterial trees. This is counterintuitive. There is ample evidence that the presence of a high Coronary Artery Calcium score (CAC) or age-and sex-inappropriate Carotid Intimal Media Thickness (CIMT) predicts higher risk of ASCVD events. Even absent the copious data we have accumulated, doesn’t it make physiologic sense to ascribe as much value to disease in the vascular beds that are direct culprits for the very events we are attempting to thwart as we do to distant arteries in the legs? I will continue to use CIMT and CAC (and coronary CT angiography) in intermediate risk patients as tools to risk reclassify patients.

The age limits of 40 to 75 are problematic. What do we do with a 35 year old woman with no other ASCVD risks except an LDL-C of 180 mg/dL and a powerful family history of premature ASCVD? Her 10 year risk is only 1.6% but she is too young to be treated by the new guidelines regardless of her risk score. I would unequivocally treat this woman.

The absence of a significant lipoprotein and triglyceride discussion relegates the guidelines to be strictly statin/LDL-C documents. They do not attempt to be comprehensive and the authors acknowledge this fact. Thus, we should not be misled to believe that lipoproteins and triglycerides are suddenly unimportant. They are not. I will continue to assess them and manage them in a patient-centric, individualized manner. Again, every patient is different. Each one deserves his or her unique assessment and management. “One size fits all” has no place in modern medicine.

Biological markers like Lipoprotein Associated Phospholipase A2 (LpPLA2), myeloperoxidase (MPO), oxidized LDL, Lp(a), and urine microalbumin have numerous studies either validating their position as ASCVD risk factors or at least implicating them in ASCVD. Though de-emphasized in these guidelines, biological markers are helpful tools in understanding our patients’ risks as well as motivating our patients to adjust their lifestyles and take their medications. I will continue to utilize them in my practice of “Interventional Prevention.”

In summation let us remember that these guidelines are not law. They are based entirely upon a mere 25 “highest level” clinical trials, ignoring thousands of “lower level” trials, human biology and physiology, and clinical acumen. To some extent I would say they are so limited in scope by inappropriately-stringent data-entry criteria that they have become Ivory Tower, clinically-blind advice. Their very construct diminishes their real world relevance. Ironically the system suggested in the guidelines has itself never been validated by the very type of RCT evidence demanded by the guideline authors. Something is surely wrong with that. Yet on a positive note the new guidelines are simpler than ATP3. Reliance more upon Global (Total) Risk rather than individual risk factors makes it easier for clinicians to make recommendations. Still, simple is not always good. As outlined above, I intend to use the guidelines as a foundation upon which to build a more dynamic and plastic way to approach the patients in my clinical practice. I refuse to await trials that may never appear. Instead, I will continue to avidly follow the literature, eagerly learn from my colleagues, and diligently incorporate a wide gamut of data to render the well-considered recommendations I ultimately share with my patients.

In the initial days of thrombolytic therapy (potent blood thinners used to treat heart attack patients) we had a saying that, “Time is Muscle”. The intent was of course to get our patients treated as quickly as possible, understanding that the longer their arteries remained closed, the more heart muscle would be lost. More damage meant worse outcomes. And so we got faster and faster, ultimately treating our patients within minutes of their initial evaluation. This need for speed has been brought into the era of acute interventions, the stents. Now we speak of door to balloon times and all hospitals boasts of their superior swiftness. The faster we get our patients to the cardiac catheterization lab for definitive treatment to stop their heart attacks, the better they do.

Analogous to the situation with heart attack patients, individuals with extremely high LDL cholesterol are now known to develop plaques in their arteries in accord with the duration that they experience their high lipid levels. Some children have such high cholesterol levels starting even from when they’re in utero; they develop heart attacks before the age of five. This of course is quite rare, but it does illustrate the importance of both cholesterol levels and time in plaque formation. For proper prevention we need to adopt a greater sense of urgency, one that embodies our understanding that the longer one has high cholesterol levels, the more likely he or she is to develop vascular disease. In short, we ought to start declaring, “Time is plaque!”

September is National Cholesterol Education Month. In support of this important educational initiative we are republishing our six part series on cholesterol and the role it plays in cardiovascular disease.

Note: Seventy-one million American adults have high cholesterol, but it is estimated that only one-third of them have the condition under control.

Today’s final post in my six-part series on cholesterol examines one FDA approved non-medication treatment for severely elevated LDL cholesterol, and three novel medications on the horizon.

LDL-Apheresis is a non-drug therapy for patients with vascular disease and LDL-C > 200. It is reserved for patients with a genetic disorder called Familial Hypercholesterolemia (FH), or those individuals who cannot tolerate standard medications but still have very high LDL levels. Therefore, this treatment is clearly not for everyone. In a manner similar to dialysis, patients are connected to a filtering machine through two IV lines. Blood is withdrawn from one arm, circulated through a series of filters and returned to the body through the other arm. Typically the procedure is performed every other week. Each treatment results in a 60% to 80% reduction in LDL particles. After treatments, the LDL will rise steadily until it can be lowered once again with another therapy. Although LDLs do increase after a treatment, studies have demonstrated a nearly 75% reduction in cardiovascular events when patients are treated with LDL-Apheresis. Thus, LDL-Apheresis is a viable option for high risk patients. I am very fortunate to be able to run one of the forty or so centers in the USA, and I am happy to say that not only is the procedure extraordinarily well tolerated, but also the lipid effects are nothing short of remarkable.

As for the medications on the horizon, three deserve immediate recognition: Mipomersen, Lomitapide, and REGN727. These are all currently “experimental” but deserve mention not just because they will likely soon be on the market, but because each one represents a truly fresh way to lower LDL.

Mipomersen, licensed by Genzyme, is a second generation antisense oligonucleotide that is administered weekly by injection. It dramatically lowers LDL. The English translation is that this drug thwarts our body’s LDL production mechanism at the DNA level. DNA’s job is to produce mRNA in order to translate DNA’s protein-producing knowledge into the actual creation of proteins. Mipomerson binds and inactivates the mRNA that carries the code for the essential protein in every LDL particle, apoB. Without apoB, LDL cannot be created. Mipomerson does not block cholesterol production; it stops our body from producing too many LDL particles. Very different from the way statins work! Read More…